Wierda William, O'brien Susan, Faderl Stefan, Ferrajoli Alessandra, Wang Xuemei, Do Kim-Anh, Garcia-Manero Guillermo, Thomas Deborah, Cortes Jorge, Ravandi-Kashani Farhad, Giles Francis, Lerner Susan, Kantarjian Hagop, Keating Michael
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2006 Jan 15;106(2):337-45. doi: 10.1002/cncr.21554.
Combining therapeutics with single-agent activity has improved treatment for patients with many malignancies. Debate continues about the impact of treatment on survival in patients with chronic lymphocytic leukemia (CLL). Purine analogues are the most active agents for treatment of patients with CLL. Recently, it was shown that a chemoimmunotherapy regimen combining fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) was very effective in treating patients with recurrent and/or refractory CLL. The objective of the current analysis was to determine whether improvements in treatment have had an impact on survival for patients with CLL.
Three nonoverlapping, sequential groups of patients enrolled on Phase II studies who received treatment with F (n = 251 patients), FC (n = 111 patients), or FCR (n = 143 patients) were analyzed. Pretreatment characteristics, responses to treatment, and overall survival were compared.
Patients who were treated with FCR had a higher complete remission rate compared with patients who were treated with combined F and C or with F alone. Statistically significantly longer estimated median survival was noted for patients who received FCR. A Cox proportional hazards, multivariable model for overall survival that included all patients (n = 505) showed that patients who received FCR had longer survival (P < 0.0001) after adjusting for other significant (P < 0.05) pretreatment characteristics, including age, hemoglobin, beta-2 microglobulin, and the number of prior treatments.
The results of this retrospective comparison of patients with recurrent and refractory CLL indicated a higher complete remission rate and the longest estimated survival for patients who were treated with FCR, providing the basis for randomized clinical trials of this regimen.
将具有单药活性的疗法联合应用已改善了多种恶性肿瘤患者的治疗效果。关于治疗对慢性淋巴细胞白血病（CLL）患者生存的影响，争论仍在继续。嘌呤类似物是治疗CLL患者最有效的药物。最近，有研究表明，一种联合氟达拉滨（F）、环磷酰胺（C）和利妥昔单抗（R）的化疗免疫疗法方案（FCR）在治疗复发和/或难治性CLL患者方面非常有效。本次分析的目的是确定治疗的改善是否对CLL患者的生存产生了影响。
对参加II期研究的三组不重叠、连续的患者进行了分析，这些患者分别接受了F治疗（n = 251例患者）、FC治疗（n = 111例患者）或FCR治疗（n = 143例患者）。比较了预处理特征、治疗反应和总生存期。
与接受F和C联合治疗或仅接受F治疗的患者相比，接受FCR治疗的患者完全缓解率更高。接受FCR治疗的患者的估计中位生存期在统计学上显著更长。一个包括所有患者（n = 505）的Cox比例风险多变量总生存模型显示，在调整了其他显著（P < 0.05）的预处理特征，包括年龄、血红蛋白、β2微球蛋白和既往治疗次数后，接受FCR治疗的患者生存期更长（P < 0.0001）。
本次对复发和难治性CLL患者的回顾性比较结果表明，接受FCR治疗的患者完全缓解率更高，估计生存期最长，为该方案的随机临床试验提供了依据。
